, Volume 17, Issue 4, pp 439–449 | Cite as

Pediatric endocrinology: an overview of the last decade

  • Lourdes IbáñezEmail author
  • Konstantina Barouti
  • Georgios K. Markantes
  • Anastasia K. Armeni
  • Neoklis A. Georgopoulos


Over the past decade, considerable progress has been made in the field of pediatric endocrinology. However, there is still a long way to go regarding the exploration of novel avenues, such as epigenetics, the changing views on the pathophysiology and derived therapy of specific disorders, and the prevention of prevalent diseases. The next decade will hopefully bring the consolidation of most of those achievements and the development of new pathways for further progress.


Pediatric endocrinology 


Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.


  1. 1.
    Oron T, Lebenthal Y, de Vries L, Yackobovitch-Gavan M, Phillip M, Lazar L (2012) Interrelationship of extent of precocious adrenarche in appropriate for gestational age girls with clinical outcome. J Pediatr 160:308–313CrossRefGoogle Scholar
  2. 2.
    Deng X, Li W, Luo Y, Liu S, Wen Y, Liu Q (2017) Association between small fetuses and puberty timing: a systematic review and meta-analysis. Int J Environ Res Public Health 14(11)Google Scholar
  3. 3.
    Uçar A, Yackobovitch-Gavan M, Erol OB et al (2014) Associations of size at birth and postnatal catch-up growth status with clinical and biomedical characteristics in prepubertal girls with precocious adrenarche: preliminary results. J Clin Endocrinol Metab 99:2878–2886CrossRefGoogle Scholar
  4. 4.
    de Zegher F, Reinehr T, Malpique R, Darendeliler F, López-Bermejo A, Ibáñez L (2017) Reduced prenatal weight gain and/or augmented postnatal weight gain precedes polycystic ovary syndrome in adolescent girls. Obesity 25:1486–1489CrossRefGoogle Scholar
  5. 5.
    de Zegher F, GarcíaBeltrán C, López-Bermejo A, Ibáñez L (2018) Metformin for rapidly maturing girls with central adiposity: less liver fat and slower bone maturation. Horm Res Paediatr 89:136–140CrossRefGoogle Scholar
  6. 6.
    Ibáñez L, López-Bermejo A, Díaz M, Marcos MV, de Zegher F (2011) Early metformin therapy (age 8–12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence. J Clin Endocrinol Metab 96:E1262–E1267CrossRefGoogle Scholar
  7. 7.
    Abreu AP, Dauber A, Macedo DB et al (2013) Central precocious puberty caused by mutations in the imprinted gene MKRN3. N Engl J Med 368:2467–2475CrossRefGoogle Scholar
  8. 8.
    Hagen CP, Sørensen K, Mieritz MG, Johannsen TH, Almstrup K, Juul A, 2015 Circulating MKRN3 levels decline prior to pubertal onset and through puberty: a longitudinal study of healthy girls. J Clin Endocrinol Metab100:1920–1926Google Scholar
  9. 9.
    Busch AS, Hagen CP, Almstrup K, Juul A (2016) Circulating MKRN3 levels decline during puberty in healthy boys. J Clin Endocrinol Metab 101:2588–2593CrossRefGoogle Scholar
  10. 10.
    Silverman LA, Neely EK, Kletter GB et al (2015) Long-term continuous suppression with once-yearly histrelin subcutaneous implants for the treatment of central precocious puberty: a final report of a phase 3 multicenter trial. J Clin Endocrinol Metab 100:2354–2363CrossRefGoogle Scholar
  11. 11.
    Lazar L, Meyerovitch J, de Vries L, Phillip M, Lebenthal Y (2014) Treated and untreated women with idiopathic precocious puberty: long-term follow-up and reproductive outcome between the third and fifth decades. Clin Endocrinol 80:570–576CrossRefGoogle Scholar
  12. 12.
    Lazar L, Lebenthal Y, Yackobovitch-Gavan M, et al, 2015 Treated and untreated women with idiopathic precocious puberty: BMI evolution, metabolic outcome, and general health between third and fifth decades. J Clin Endocrinol Metab100:1445–1451Google Scholar
  13. 13.
    Howard SR, Guasti L, Ruiz-Babot G et al (2016) IGSF10 mutations dysregulate gonadotropin-releasing hormone neuronal migration resulting in delayed puberty. EMBO Mol Med 8:626–642CrossRefGoogle Scholar
  14. 14.
    Howard SR, Guasti L, Poliandri A et al (2018) Contributions of function-altering variants in genes implicated in pubertal timing and body mass for self-limited delayed puberty. J Clin Endocrinol Metab 103:649–659CrossRefGoogle Scholar
  15. 15.
    Ibáñez L, Oberfield SE, Witchel S et al (2017) An international consortium update: pathophysiology, diagnosis, and treatment of polycystic ovarian syndrome in adolescence. Horm Res Paediatr 88:371–395CrossRefGoogle Scholar
  16. 16.
    Anderson AD, Solorzano CM, McCartney CR (2014) Childhood obesity and its impact on the development of adolescent PCOS. Semin Reprod Med 32:202–213CrossRefGoogle Scholar
  17. 17.
    Lass N, Kleber M, Winkel K, Wunsch R, Reinehr T (2011) Effect of lifestyle intervention on features of polycystic ovarian syndrome, metabolic syndrome, and intima-media thickness in obese adolescent girls. J Clin Endocrinol Metab 96:3533–3540CrossRefGoogle Scholar
  18. 18.
    Ibáñez L, del Río L, Díaz M et al (2017) Normalizing ovulation rate by preferential reduction of hepato-visceral fat in adolescent girls with polycystic ovary syndrome. J Adolesc Health 61:446–453CrossRefGoogle Scholar
  19. 19.
    Levy-Marchal C, Arslanian S, Cutfield W et al (2010) Insulin resistance in children: consensus, perspective, and future directions. J Clin Endocrinol Metab 95:5189–5198CrossRefGoogle Scholar
  20. 20.
    Gluckman PD, Hanson MA, Cooper C, Thornburg KL (2008) Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 359:61–73CrossRefGoogle Scholar
  21. 21.
    Voerman E, Jaddoe VW, Franco OH, Steegers EA, Gaillard R (2017) Critical periods and growth patterns from fetal life onwards associated with childhood insulinlevels. Diabetologia 60:81–88CrossRefGoogle Scholar
  22. 22.
    Ogden CL, Carroll MD, Kit BK, Flegal KM (2014) Prevalence of childhood and adult obesity in the United States, 2011–2012. 311:806–814Google Scholar
  23. 23.
    Preventive Services Task Force US, Grossman DC, Bibbins-Domingo K, Curry SJ et al (2017) Screening for obesity in children and adolescents: US Preventive Services Task Force recommendation statement. JAMA 317:2417–2242CrossRefGoogle Scholar
  24. 24.
    Reinehr T, Lass N, Toschke C, Rothermel J, Lanzinger S, Holl RW (2016) Which amount of BMI-SDS reduction is necessary to improve cardiovascular risk factors in overweight children? J Clin Endocrinol Metab 101:3171–3179CrossRefGoogle Scholar
  25. 25.
    Baird J, Fisher D, Lucas P, Kleijnen J, Roberts H, Law C (2005) Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ 331:929CrossRefGoogle Scholar
  26. 26.
    Druet C, Stettler N, Sharp S et al (2012) Prediction of childhood obesity by infancy weight gain: an individual-level meta-analysis. Paediatr Perinat Epidemiol 26:19–26CrossRefGoogle Scholar
  27. 27.
    Elks CE, Heude B, de Zegher F et al (2014) Associations between genetic obesity susceptibility and early postnatal fat and lean mass: an individual participant meta-analysis. JAMA Pediatr 168:1122–1130CrossRefGoogle Scholar
  28. 28.
    Díaz M, García C, Sebastiani G, de Zegher F, López-Bermejo A, Ibáñez L (2017) Placental and cord blood methylation of genes involved in energy homeostasis: association with fetal growth and neonatal body composition. Diabetes 66:779–784CrossRefGoogle Scholar
  29. 29.
    Dabelea D, Mayer-Davis EJ, Saydah S et al (2009) Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to. JAMA 311:1778–1786CrossRefGoogle Scholar
  30. 30.
    Onkamo P, Väänänen S, Karvonen M, Tuomilehto J (1999) Worldwide increase in incidence of type I diabetes—the analysis of the data on published incidence trends. Diabetologia 42:1395–1403CrossRefGoogle Scholar
  31. 31.
    Mayer-Davis EJ, Lawrence JM, Dabelea D et al (2017) Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012. N Engl J Med 376:1419–1429CrossRefGoogle Scholar
  32. 32.
    Dabelea D, Stafford JM, Mayer-Davis EJ et al (2017) Association of type 1 diabetes vs type 2 diabetes diagnosed during childhood and adolescence with complications during teenage years and young adulthood. JAMA 317:825–835CrossRefGoogle Scholar
  33. 33.
    Chrysis D, Efthymiadou A, Mermigka A, Kritikou D, Spiliotis BE (2017) Osteoprotegerin, RANKL, ADMA, and Fetuin-A serum levels in children with type I diabetes mellitus. Pediatr Diabetes 18:277–282CrossRefGoogle Scholar
  34. 34.
    Dabelea D, Mayer-Davis EJ, Lamichhane AP et al (2008) Association of intrauterine exposure to maternal diabetes and obesity with type 2 diabetes in youth. Diabetes Care 31:1422–1426CrossRefGoogle Scholar
  35. 35.
    van der Steen I, van Albada ME, Mohnike K et al (2018) A multicenter experience with long-acting somatostatin analogues in patients with congenital hyperinsulinism. Horm Res Paediatrics 89:82–89CrossRefGoogle Scholar
  36. 36.
    Senniappan S, Alexandrescu S, Tatevian N et al (2014) Sirolimus therapy in infants with severe hyperinsulinemic hypoglycemia. N Engl J Med 370:1131–1137CrossRefGoogle Scholar
  37. 37.
    Maynika V Rastogi and Stephen H LaFranchi (2010) Congenital hypothyroidism Orphanet J Rare Dis. 1186/1750-1172-5-17
  38. 38.
    Léger L, Olivieri A, Donaldson M et al (2014) European Society for Paediatric Endocrinology Consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab 99:363–384CrossRefGoogle Scholar
  39. 39.
    Mengreli C, Kanaka-Gantenbein C, Girginoudis P (2010) Screening for congenital hypothyroidism: the significance of threshold limit in false-negative results. J Clin Endocrinol Metab 95:4283–4290CrossRefGoogle Scholar
  40. 40.
    Wasniewska M, Salerno M, Cassio A et al (2009) Prospective evaluation of the natural course of idiopathic subclinical hypothyroidism in childhood and adolescence. Eur J Endocrinol 160:417–422CrossRefGoogle Scholar
  41. 41.
    Bochukova E, Schoenmakers N, Agostini M et al (2012) A mutation in the thyroid hormone receptor alpha gene. N Engl J Med 366:243–249CrossRefGoogle Scholar
  42. 42.
    Gupta A, Ly S, Castroneves LA, Frates MC et al (2013) A standardized assessment of thyroid nodules in children confirms higher cancer prevalence than in adults. J Clin Endocrinol Metab 98:3238–3245CrossRefGoogle Scholar
  43. 43.
    Hogan AR, Zhuge Y, Perez EA, Koniaris LG, Lew JI, Sola JE (2009) Pediatric thyroid carcinoma: incidence and outcomes in 1753 patients. J Surg Res 156:167–172CrossRefGoogle Scholar
  44. 44.
    Francis GL, Waguespack SG, Bauer AJ, American Thyroid Association Guidelines Task Force et al (2015) Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid 25:716–759CrossRefGoogle Scholar
  45. 45.
    Speiser PW, Azziz R, Baskin LS et al (2010) Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 95:4133–4160CrossRefGoogle Scholar
  46. 46.
    Miller WL, Witchel SF (2013) Prenatal treatment of congenital adrenal hyperplasia: risks outweigh benefits. Am J Obstet Gynecol 208:354–359CrossRefGoogle Scholar
  47. 47.
    Wallensteen L, Zimmermann M, Thomsen Sandberg M, Gezelius A, Nordenström A, Hirvikoski T, Lajic S (2016) Sex-dimorphic effects of prenatal treatment with dexamethasone. J Clin Endocrinol Metab 101:3838–3846CrossRefGoogle Scholar
  48. 48.
    Tardy-Guidollet V, Menassa R, Costa JM et al (2014) New management strategy of pregnancies at risk of congenital adrenal hyperplasia using fetal sex determination in maternal serum: French cohort of 258 cases (2002–2011). J Clin Endocrinol Metab 99:1180–1188CrossRefGoogle Scholar
  49. 49.
    Livadas S, Dracopoulou M, Dastamani A et al (2015) The spectrum of clinical, hormonal and molecular findings in 280 individuals with nonclassical congenital adrenal hyperplasia caused by mutations of the CYP21A2 gene. Clin Endocrinol 82:543–549CrossRefGoogle Scholar
  50. 50.
    Lee PA, Nordenström A, Houk CP et al (2016) Global DSD Update Consortium. Global disorders of sex development update since 2006: perceptions, approach, and care. Horm Res Paediatr 85:158–180CrossRefGoogle Scholar
  51. 51.
    Arboleda VA, Lee H, Sánchez FJ et al (2013) Targeted massively parallel sequencing provides comprehensive genetic diagnosis for patients with disorders of sex development. Clin Genet 83:35–43CrossRefGoogle Scholar
  52. 52.
    Cox K, Bryce J, Jiang J et al (2014) Novel associations in disorders of sex development: findings from the I-DSD Registry. J Clin Endocrinol Metab 99:E348–E355CrossRefGoogle Scholar
  53. 53.
    Fénichel P, Paris F, Philibert P et al (2013) Molecular diagnosis of 5α-reductase deficiency in 4 elite young female athletes through hormonal screening for hyperandrogenism. J Clin Endocrinol Metab 98:E1055–E1059CrossRefGoogle Scholar
  54. 54.
    Rosenthal SM (2014) Approach to the patient: transgender youth: endocrine considerations. J Clin Endocrinol Metab 99:4379–4389CrossRefGoogle Scholar
  55. 55.
    Hembree WC, Cohen-Kettenis PT, Gooren L et al (2017) Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 102:3869–3903CrossRefGoogle Scholar
  56. 56.
    Schlingmann KP, Kaufmann M, Weber S et al (2011) Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med 365:410–421CrossRefGoogle Scholar
  57. 57.
    Whyte MP, Greenberg CR, Salman NJ et al (2012) Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med 366:904–913CrossRefGoogle Scholar
  58. 58.
    Lee NK, Sowa H, Hinoi E et al (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469CrossRefGoogle Scholar
  59. 59.
    Oury F, Sumara G, Sumara O et al (2011) Endocrine regulation of male fertility by the skeleton. Cell 144:796–809CrossRefGoogle Scholar
  60. 60.
    Bell J, Parker KL, Swinford RD, Hoffman AR, Maneatis T, Lippe B (2010) Long-term safety of recombinant human growth hormone in children. J Clin Endocrinol Metab 95:167–177CrossRefGoogle Scholar
  61. 61.
    Blum WF, Ross JL, Zimmermann AG et al (2013) GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial. J Clin Endocrinol Metab 98:E1383–E1392CrossRefGoogle Scholar
  62. 62.
    Grimberg A, DiVall SA, Polychronakos C, Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society et al (2016) Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr 86:361–397CrossRefGoogle Scholar
  63. 63.
    Gravholt CH, Andersen NH, Conway GS, International Turner Syndrome Consensus Group et al (2017) Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol 177:G1–G70CrossRefGoogle Scholar
  64. 64.
    Wakeling EL, Brioude F, Lokulo-Sodipe O et al (2017) Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol 13:105–124CrossRefGoogle Scholar
  65. 65.
    Chatelain P, Malievskiy O, Radziuk K, TransCon GH Working Group et al (2017) A randomized phase 2 study of long-acting TransCon GH vs daily GH in childhood GH deficiency. J Clin Endocrinol Metab 102:1673–1682CrossRefGoogle Scholar
  66. 66.
    Hauer NN, Sticht H, Boppudi S et al (2017) Genetic screening confirms heterozygous mutations in ACAN as a major cause of idiopathic short stature. Sci Rep 7:12225CrossRefGoogle Scholar
  67. 67.
    Gibson BG, Briggs MD (2016) The aggrecanopathies; an evolving phenotypic spectrum of human genetic skeletal diseases. Orphanet J Rare Dis 11:86CrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2018

Authors and Affiliations

  • Lourdes Ibáñez
    • 1
    • 2
    Email author
  • Konstantina Barouti
    • 3
  • Georgios K. Markantes
    • 3
  • Anastasia K. Armeni
    • 1
    • 3
  • Neoklis A. Georgopoulos
    • 1
    • 3
  1. 1.Pediatric Research Institute Sant Joan de DeuUniversity of Barcelona, Esplugues, Barcelona, Spain & CIBERDEM, Instituto de Salud Carlos IIIMadridSpain
  2. 2.Hospital Sant Joan de DéuUniversity of BarcelonaBarcelonaSpain
  3. 3.Division of Reproductive Endocrinology, Department of Obstetrics and GynecologyUniversity of Patras Medical SchoolPatrasGreece

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